Nephron最新文献

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent hereditary kidney disease and the fourth most common cause of kidney failure. Patients may be aware of their condition from an early age or discover it unexpectedly, with varying levels of familial knowledge about the disease. This chronic condition presents significant challenges for healthcare professionals. The study aimed to investigate how people with ADPKD experience their participation in a dedicated ADPKD clinic and to investigate their support needs in managing their disease in everyday life.

Methods: A qualitative phenomenological descriptive study was conducted, involving semi-structured telephone interviews with patients who attended a newly established dedicated ADPKD clinic between March and April 2023. The data were analyzed using Malterud's principles of systematic text condensation.

Results: In total, 18 out of 22 patients agreed to participate in the interviews. Six themes emerged from the interviews. Participants expressed feelings of uncertainty about their future and highlighted the necessity for personalized care tailored to their individual circumstances. They reported challenges in coping with emotions associated with the disease and sought assistance in making difficult decisions. Maintaining control over their health and illness was a significant theme, alongside a desire for increased knowledge about their condition.

Conclusion: Our study supports existing knowledge in this area. In this study, the participants experienced satisfaction with the dedicated ADPKD clinic, feeling well informed, listened to, and more at ease after the check-up. Investing in a dedicated ADPKD clinic could help alleviate the uncertainty that many people with ADPKD experience.

The ultimate goal of precision medicine is to tailor treatment to specific disease processes, thereby optimising patient outcomes. This approach moves beyond the one-size-fits-all model, recognising at an individual level the unique combinations of molecular, genetic, and environmental factors determining disease progression and treatment response. Chronic kidney disease (CKD) exemplifies the need for precision medicine, given its complex and heterogeneous nature. Traditional biomarkers, such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR), have long been the cornerstone of CKD diagnosis and management. However, these markers homogenise a diverse group of distinct conditions within CKD with separate pathophysiologies and progression rates. The standardisation of CKD definition has improved clarity and consistency but has inadvertently led to a generic classification system, which categorises patients with CKD based on these non-specific markers and fails to capture the nuances of individual patient conditions. As a result, there is a critical need for novel biomarkers that can more accurately represent specific aetiologies and mechanisms of CKD progression. By identifying and utilising novel biomarkers, the field of nephrology could better understand individual mechanisms of CKD progression and move towards tailored risk prediction and treatment strategies, ultimately improving patient outcomes. This review is not intended to be a comprehensive review of all biomarkers in CKD but a proposal to the nephrology community to think more pathophysiologically about CKD, recognise the importance of distinct primary kidney diseases, and start working towards a more personalised medicine approach.

Background and hypothesis: Efficient arteriovenous access (VA) surveillance is vital for early identification of dysfunctional access, allowing timely intervention to prevent thrombosis. This study compares the efficacy of adding remote software surveillance to standard clinical care across our units.

Methods: We conducted a 12-month prospective study on maintenance hemodialysis (HD) patients using Vasc-Alert software technology to assist clinical decision-making in 2 satellite HD units (Group 1) and standard care in the remaining 3 HD units (Group 2) . Patients with Vasc-alert derived high Access Risk Score (ARS) (≥7) underwent clinical assessment and were referred for fistulogram based on relevant Kidney Disease Outcome Quality Initiative (KDOQI) criteria. Data on referrals for fistulogram, subsequent VA events, access abandonment, and complication-free days- extended (CFD-extended) were collected.. VA survival analysis of post-intervention primary patency rate at 3 and 6 months was conducted.

Results: There were 23 (28.1%) preemptive correction of stenosis and 6 (7.3%) thrombosis episodes in Group 1, compared to 40 (19.5%)and 21 (10.2%) in Group 2 (p value 0.155, 0.587),respectively). Amongst the thrombotic episodes, 83% of cases in Group 1 had been detected during surveillance and referred for diagnostic fistulogram +/- angioplasty but developed thrombosis whilst awaiting elective intervention compared to 19% in Group 2 (P value = 0.004). Median time from fistulogram request to thrombosed VA was 26 days (IQR 21-42 days).Group 1 exhibited better post-intervention primary patency rates and longer CFD compared to Group 2 (p value < 0.001, 0.002, respectively).

Conclusion: Incorporating Vasc-Alert technology into VA clinical surveillance pathway was associated with improved early detection of high-risk VA, higher primary patency rates, and longer CFD-extended compared to standard of care. Improving elective interventional radiology (IR) capacity for timely intervention (< 3 weeks from referral) is crucial to materialise the benefits of enhanced surveillance in preventing acute thrombosis.

Background: With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN.

Methods: We conducted a comprehensive bidirectional Mendelian randomization (MR) study. We selected 211 bacterial taxa using Genome-wide association study (GWAS) data provided by the MiBioGen consortium, while GWAS data relevant to MN were obtained from ebi-a-GCST010005. The inverse-variance weighted (IVW) method was the primary technique used to delineate the causal relationship between exposures and outcomes. To confirm the robustness of our results, we used additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses included tests for pleiotropy, heterogeneity, and leave-one-out sensitivity to ensure the integrity of our conclusions. Finally, reverse MR analyses were conducted to assess the likelihood of reverse causality.

Results: Using various analytical methods, including the IVW approach, MR-Egger, weighted median, simple mode, and weighted mode, our study identified six microbial taxa with a statistically significant causal link to MN, as indicated by p-values less than 0.05. The implicated taxa are Butyrivibrio (OR= 1.25, 95 % CI: 1.001-1.565, P = 0.048), Butyricicoccus (OR = 2.15, 95 % CI: 1.005-4.621, P = 0.048), Catenibacterium (OR = 1.49, 95 % CI: 1.043-2.134, P = 0.028), Ruminiclostridium5 (OR = 1.78, 95 % CI: 1.140-2.763, P = 0.03), RuminococcaceaeUCG003 (OR = 1.78, 95 % CI: 1.140-2.763, P = 0.011) and Bacillales (OR = 1.52, 95 % CI: 1.135-2.025, P = 0.005). Each of these taxa has been established as a risk factor for MN. Notably, Ruminococcaceae UCG-003 and Bacillales were identified as having a bidirectional causal relationship with the disease.

Conclusion: Our MR study has revealed a causal link between six microbial taxa and MN, highlighting their potential involvement in the disease's development. These findings represent an initial step into this complex field and underscore the need for more in-depth research.

Background: The recurrence of primary glomerulonephritis (GN) following kidney transplantation poses a significant threat to graft survival. To enhance kidney transplant outcomes, we must lessen the burden of recurrence. In recent years, there has been progress in understanding the incidence, risk factors for recurrence, pathophysiology, biomarkers, and therapeutics, making it worthwhile to conduct an update on primary glomerulonephritis that may recur following kidney transplantation.

Summary: We conducted a narrative review of the literature on the novel discoveries of primary GN that can recur following kidney transplantation. To summarize, developing a broad consensus on recurrence diagnosis would greatly advance our understanding, and its development would be a valuable collaborative effort. The key risk factors for recurrence have been better understood, particularly in individuals with complement-related or monoclonal gammopathy-related recurrent membranoproliferative glomerulonephritis. Furthermore, we can identify better recurrent IgA nephropathy patients who are more likely to experience graft loss. New biomarkers for membranous nephropathy (anti-PLA2R-Ab) and focal and segmental glomerulosclerosis (anti-nephrin-Ab) can assist in identifying and monitoring patients at risk of recurrence. Regarding therapy, the focal and segmental glomerulosclerosis consensus will enhance recurrence treatment. Some complement inhibitors and anti-CD38 monoclonal antibodies are already promising in treating and healing recurrent C3 glomerulopathy and focal and segmental glomerulosclerosis, respectively. Finally, new drugs developed specifically to treat IgA nephropathy in the native kidney will also change the outcome of IgA nephropathy recurrence.

Key messages: Although there has been progress in understanding the recurrence of primary glomerulonephritis following kidney transplantation, a worldwide effort should be undertaken to gather research that will allow for improved diagnosis, monitoring, and management of these patients.

Introduction: The efficacy of telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of telitacicept in patients with IgAN.

Methods: This study recruited patients with IgAN from 19 sites from China who were treated with telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021, to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time.

Results: A cohort of 97 patients with IgAN who were treated with telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] mL/min/1.73 m2. There was a significant reduction of proteinuria at 2, 4, 6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5, 1.7] g/day, all p values <0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] mL/min/1.73 m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] mL/min/1.73 m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] mL/min/1.73 m2, all p values >0.26). Telitacicept was well tolerated in the patients.

Conclusions: This study indicates that telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still needs to be confirmed in large phase III trial.

Background: The lysosomal autophagic pathway plays a fundamental role in cellular and tissue homeostasis, and its deregulation is linked to human pathologies including kidney diseases. Autophagy can randomly degrade cytoplasmic components in a nonselective manner commonly referred to as bulk autophagy. In contrast, selective forms of autophagy specifically target cytoplasmic structures such as organelles and protein aggregates, thereby being important for cellular quality control and organelle homeostasis.

Summary: Research during the past decades has begun to elucidate the role of selective autophagy in kidney physiology and kidney diseases.

Key messages: In this review, we will summarize the knowledge on lipophagy and mitophagy, two forms of selective autophagy important in renal epithelium homeostasis, and discuss how their deregulations contribute to renal disease progression.

Diabetic kidney disease is the most common driver of chronic kidney disease (CKD)-associated mortality and kidney replacement therapy. Despite recent therapeutic advances (sodium glucose co-transporter 2 [SGLT2] inhibitors, finerenone), the residual kidney and mortality risk remains high for patients already diagnosed of having CKD (i.e., estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio >30 mg/g). The challenge for the near future is to identify patients at higher risk of developing CKD to initiate therapy before CKD develops (primary prevention of CKD) and to identify patients with CKD and high risk of progression or death, in order to intensify therapy. We now discuss recent advances in biomarkers that may contribute to the identification of such high-risk individuals for clinical trials of novel primary prevention or treatment approaches for CKD. The most advanced biomarker from a clinical development point of view is the urinary peptidomics classifier CKD273, that integrates prognostic information from 273 urinary peptides and identifies high-risk individuals before CKD develops.